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Molecular Pharmacology

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Abstract

5-Hydroxytryptamine type 2A and 2C receptors linked to Na+/K+/Cl- cotransport.

S E Mayer and E Sanders-Bush
Molecular Pharmacology May 1994, 45 (5) 991-996;
S E Mayer
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Abstract

The goal of the present paper was to investigate 5-hydroxytryptamine (5HT)2A and 5HT2C receptor regulation of ion transport in fibroblast cell lines transfected with these receptors. Na+/K(+)-ATPase and Na+/K+/2Cl- cotransport were measured with 86Rb+ as a surrogate for K+ uptake. Serotonin agonists had no effect on Na+/K(+)-ATPase activity in either cell line. Bumetanide, an antagonist of Na+/K+/2Cl- cotransport, almost completely blocked ouabain-insensitive K+ uptake in both cell lines, with an IC50 of about 1 microM. 36Cl- uptake was 2-fold greater than 86Rb+ uptake, consistent with the expected 2:1 stoichiometry. In addition, the Cl-/HCO3- uptake blocker 4,4'-diisothiostilbene-2,2'-disulfonic acid had no effect on Cl- uptake. The 5HT2A/2C receptor agonist (-)-2,5-dimethoxy-4-bromoamphetamine increased ouabain-insensitive K+ uptake, and this effect was blocked by bumetanide. The receptor antagonists mianserin and mesulergine, but not spiperone, blocked (-)-2,5-dimethoxy-4-bromoamphetamine responses in fibroblasts transfected with 5HT2C receptors, and all three antagonists blocked the effects in cells expressing 5HT2A receptors. Ouabain-insensitive 22Na+ uptake was similarly affected. 5HT receptor-related actions were not observed in untransfected parent NIH/3T3 fibroblasts. Thus, we have demonstrated that 5HT2C and 5HT2A receptors are linked to activation of Na+/K+/2Cl- cotransport in transfected fibroblasts. This activity may be a factor in the pharmacological actions of 5HT agonists and antagonists.

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Molecular Pharmacology
Vol. 45, Issue 5
1 May 1994
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Abstract

5-Hydroxytryptamine type 2A and 2C receptors linked to Na+/K+/Cl- cotransport.

S E Mayer and E Sanders-Bush
Molecular Pharmacology May 1, 1994, 45 (5) 991-996;

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Abstract

5-Hydroxytryptamine type 2A and 2C receptors linked to Na+/K+/Cl- cotransport.

S E Mayer and E Sanders-Bush
Molecular Pharmacology May 1, 1994, 45 (5) 991-996;
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